The dependence of neurons on tropic molecules for survival during development is a fundamental theme in neurobiology. A major unanswered question about this trophic relationship is whether neuronal form is regulated by these same signals. A second question, which has relevance to neurodegenerative diseases, is to what extent neurons in mature animals remain dependent. I propose to investigate these issues in vivo using motor neurons and sympathetic ganglion cells as model systems. Four specific questions will be addressed. First, the effects of nerve growth factor (NGF) and anti-sera to NGF on the development of dendritic arbors and innervation of sympathetic ganglion cells will be studied. Second, the effects of target- derived factors on the dendritic arborization of somatic motor neurons will be studied by analyzing arbors after experimentally induced increases and decreases in the number of skeletal muscle fibers innervated by these neurons. Third, the morphological responses of sympathetic ganglion cells and motor neurons to trophic deprivation in maturity will be assessed. Finally, the exquisite target dependence of motor neurons in neonates will be used as a bioassay to test the trophic potential of certain tissues and pharmacological compounds. For all of these studies, dendritic arbors will be revealed by retrograde transport of ligand-conjugated tracers or by intracellular staining in tissues previously fixed by immersion or perfusion. Neuronal survival will be assessed using conventional paraffin histology and counts of myelinated ventral root axons. My long term goal is to characterize relationships necessary for the maintenance of normal motor neuron properties. The staining techniques to be developed should ultimately be applicable to human spinal cord and the assays of survival should prove useful in testing a variety of potential trophic molecules and toxins.